title: Hypothalamic oxytocin attenuates CRF expression via GABA(A) receptors in rats.
abstract: Centrally released oxytocin (OXT) has anxiolytic and anti-stress effects. Delayed gastric emptying (GE) induced by acute restraint stress (ARS) for 90 min is completely restored following 5 consecutive days of chronic homotypic restraint stress (CHS), via up-regulating hypothalamic OXT expression in rats. However, the mechanism behind the restoration of delayed GE following CHS remains unclear. Gamma-aminobutyric acid (GABA)-projecting neurons in the paraventricular nucleus (PVN) have been shown to inhibit corticotropin releasing factor (CRF) synthesis via GABA(A) receptors. We hypothesized that GABA(A) receptors are involved in mediating the inhibitory effect of OXT on CRF expression in the PVN, which in turn restores delayed GE following CHS. OXT (0.5 μg) and selective GABA(A) receptor antagonist, bicuculline methiodide (BMI) (100 ng), were administered intracerebroventricularly (icv). Solid GE was measured under non-stressed (NS), ARS and CHS conditions. Expression of CRF mRNA in the PVN was evaluated by real time RT-PCR. Neither OXT nor BMI changed GE and CRF mRNA expression under NS conditions. Delayed GE and increased CRF mRNA expression induced by ARS were restored by icv-injection of OXT. The effects of OXT on delayed GE and increased CRF mRNA expression in ARS were abolished by icv-injection of BMI. Following CHS, delayed GE was completely restored in saline (icv)-injected rats, whereas daily injection of BMI (icv) attenuated the restoration of delayed GE. Daily injection of BMI (icv) significantly increased CRF mRNA expression following CHS. It is suggested that central OXT inhibits ARS-induced CRF mRNA expression via GABA(A) receptors in the PVN. GABAergic system is also involved in OXT-mediated adaptation response of delayed GE under CHS conditions.
authors.affiliation: Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, Milwaukee, WI 53295, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bülbül
authors.forename: Reji
authors.initials: R
authors.lastname: Babygirija
authors.forename: Diana
authors.initials: D
authors.lastname: Cerjak
authors.forename: Sazu
authors.initials: S
authors.lastname: Yoshimoto
authors.forename: Kirk
authors.initials: K
authors.lastname: Ludwig
authors.forename: Toku
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D005746:Gastric Emptying / Q000502:physiology; D015870:Gene Expression; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D010121:Oxytocin / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D011963:Receptors, GABA-A; C017069:bicuculline methiodide; D010121:Oxytocin; D003346:Corticotropin-Releasing Hormone; D001640:Bicuculline